Monitoring the effects of treatment for breast cancer treatment-induced bone loss
The response to anti-resorptive therapy can be monitored in the individual by the use of bone turnover markers or BMD. The goal of monitoring the individual is to identify nonresponse.
This might indicate inadequate compliance with therapy, underlying secondary osteoporosis or simply failure of the drug to be effective.
Bone turnover markers can be used to monitor response to treatments such as the once weekly (or once monthly) bisphosphonates risedronate, alendronate and ibandronate.
The primary mechanism of action of these drugs is to reduce bone resorption, and so it is logical to use bone resorption markers. The most commonly used markers are urinary NTX expressed as a ratio to creatinine and measured on a second morning void urine sample, serum CTX on a serum sample collected between 8 and 10am with the patient in the fasting state. These markers decrease on average by 55–75%, and the maximal response is complete by about 3 months of treatment. It may be helpful to have two measurements of bone resorption marker before the treatment is started and then further measurements can be made at 3 and 6 months.
The goal of anti-resorptive treatment is to reduce the bone resorption marker by more than the least significant change, into the lower half of the reference range for healthy young women. Bone turnover markers do vary from day to day, and the least significant change approach takes this into account. A decrease of 50% or more in bone resorption markers usually indicates that the least significant change has been exceeded. It is helpful to plot out the graph to show to the patient. The lower half of the reference range is taken as the second target. Women between the age of 35 and 45 years have reached peak bone mass and have not yet started to lose bone, and so this can be considered to be a period of stable bone health. The lower part of the reference range has been associated with the lowest risk of fracture. This approach is helpful when bone turnover markers are being measured for
the first time once the patient has started treatment. Care needs to be taken when interpreting bone turnover markers, as there may be changes due to intercurrent diseases or to
recent fracture. BMD can also be used to monitor response to anti-resorptive treatments. It is usual to recommend an 18-month to 2-year interval before making the second measurement, as the increase in BMD is quite small, even at the lumbar spine (the optimal site for measurement).
The only published study of bisphosphonates in aromatase inhibitor-associated bone loss is the use of zoledronic acid in women receiving letrozole. In this study, zoledronic acid therapy was associated with a mean increase in the spine and total hip at 1 year of 4% and 3%, respectively. The best site in the proximal femur for monitoring therapy is the total hip, as this shows the least variability. Care needs to be taken in interpreting change in BMD as there may have been changes to vertebral anatomy in the intervening period, for example degenerative changes in the spine, differences in the positioning of the femur or large changes in weight. The least significant change for the spine is about 5%.
The response to anti-resorptive therapy can be monitored in the individual by the use of bone turnover markers or BMD. The goal of monitoring the individual is to identify nonresponse.
This might indicate inadequate compliance with therapy, underlying secondary osteoporosis or simply failure of the drug to be effective.
Bone turnover markers can be used to monitor response to treatments such as the once weekly (or once monthly) bisphosphonates risedronate, alendronate and ibandronate.
The primary mechanism of action of these drugs is to reduce bone resorption, and so it is logical to use bone resorption markers. The most commonly used markers are urinary NTX expressed as a ratio to creatinine and measured on a second morning void urine sample, serum CTX on a serum sample collected between 8 and 10am with the patient in the fasting state. These markers decrease on average by 55–75%, and the maximal response is complete by about 3 months of treatment. It may be helpful to have two measurements of bone resorption marker before the treatment is started and then further measurements can be made at 3 and 6 months.
The goal of anti-resorptive treatment is to reduce the bone resorption marker by more than the least significant change, into the lower half of the reference range for healthy young women. Bone turnover markers do vary from day to day, and the least significant change approach takes this into account. A decrease of 50% or more in bone resorption markers usually indicates that the least significant change has been exceeded. It is helpful to plot out the graph to show to the patient. The lower half of the reference range is taken as the second target. Women between the age of 35 and 45 years have reached peak bone mass and have not yet started to lose bone, and so this can be considered to be a period of stable bone health. The lower part of the reference range has been associated with the lowest risk of fracture. This approach is helpful when bone turnover markers are being measured for
the first time once the patient has started treatment. Care needs to be taken when interpreting bone turnover markers, as there may be changes due to intercurrent diseases or to
recent fracture. BMD can also be used to monitor response to anti-resorptive treatments. It is usual to recommend an 18-month to 2-year interval before making the second measurement, as the increase in BMD is quite small, even at the lumbar spine (the optimal site for measurement).
The only published study of bisphosphonates in aromatase inhibitor-associated bone loss is the use of zoledronic acid in women receiving letrozole. In this study, zoledronic acid therapy was associated with a mean increase in the spine and total hip at 1 year of 4% and 3%, respectively. The best site in the proximal femur for monitoring therapy is the total hip, as this shows the least variability. Care needs to be taken in interpreting change in BMD as there may have been changes to vertebral anatomy in the intervening period, for example degenerative changes in the spine, differences in the positioning of the femur or large changes in weight. The least significant change for the spine is about 5%.
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